LB-006 - ARTERIAL STIFFNESS AND SYSTEMIC VASCULAR CORRELATES OF BRAIN AMYLOIDOSIS AND PRECLINICAL AD

R. Neal¹, z. yang², M. obideen³, A. Quyyumi², j. Lah², A. Levey², I. Hajjar³; ¹UT Southwestern Medical Center, Dallas, TX, USA, ²EMORY University School of Medicine, , , ³UT Southwestern Medical Center, , .

Background: Recent studies suggest a significant role for vascular dysfunction in the pathogenesis of Alzheimer’s disease (AD). Increased aortic stiffness or subclinical atherosclerosis may antedate cardiovascular disease. However, their link to AD especially amyloid accumulation remains unknown.

Methods: Participants from The Emory Healthy Brain study (EHBS) and the Brain, Stress, Hypertension, and Aging Program (B-SHARP) were classified into four groups based on AD biomarkers and cognitive status: normal, preclinical AD, prodromal AD, and non-AD Mild Cognitive Impairment (MCI). Participants underwent systemic vascular assessments that included arterial stiffness (carotid-femoral pulse wave velocity and Analysis (PWV and PWA) measured using Sphygmocor device, Carotid Intima-Media Thickness (CIMT), and CSF biomarker measurements of Aβ42, Tau, and p-Tau. Cognitive status was determined by consensus. General Linear Model (GLM) and Logistic regression analyses were used to assess the associations between vascular phenotypes with biomarkers or the AD classification.

Results: Our study included 1300 participants with vascular and CSF biomarker measurements had an average age of 63 (SD=7), mean BMI of 26.55 (SD=4.55) kg/m2, 67% were women, and 80% were White. Our analysis after adjusting for possible confounders revealed a significant association with CSF Aβ42. In contrast there was no significant association with CSF Tau & pTau. Furthermore, we found higher PWV measurements were associated with lower levels of CSF Aβ42 by -10.67 pg/dl for each 1 m/s increase (p < 0.047). CIMT measurements were significantly correlated with Tau (p < 0.001), and pTau (p < 0.0001). Higher CIMT measurements were associated with higher levels of CSF Tau by 50.02 pg/dl (p < 0.008) and CSF pTau by 4.9 pg/dl (p < 0.009) with each 1 mm increase. The higher vascular measurements were also associated with increased odds of having pre-clinical AD for PWV (odds ratio 1.22, CI95% 1.14-1.30, AUC 0.63, p< 0.001), and CIMT (odds ratio 17.5 CI95% 5.7- 53.53, AUC 0.57, p< 0.007).

Conclusion: Vascular measurements of arterial stiffness and subclinical atherosclerosis are associated with CSF AD biomarkers and higher odds of developing AD. Vascular measurements may offer a non-invasive method for identifying individuals at high risk for being in the pre-clinical stage of AD.